Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017075 | SCV001178100 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-05 | criteria provided, single submitter | clinical testing | The p.P350S variant (also known as c.1048C>T), located in coding exon 9 of the CHEK2 gene, results from a C to T substitution at nucleotide position 1048. The proline at codon 350 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002549448 | SCV003482176 | uncertain significance | Familial cancer of breast | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 350 of the CHEK2 protein (p.Pro350Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 822045). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |